Impact of Risk Factors and

Background:We know from the literature that certain patients are at higher risk for postoperative recurrence based on previously described adverse prognostic features. This prospective study was performed to determine:

The validity of these previously defined risk groups and

Whether the total therapy time was an important factor in determining local-regional control and overall survival.

Theoretically, gains in local control may be achieved by decreasing treatment time and offsetting the rapid repopulation of microscopic, postoperative tumor foci.

Materials and Methods:Two hundred eighty-eight patients with locally advanced sqamous cell carcinoma of the head and neck were prspectively registered in this trial. They underwent radical surgery and were then defined by risk groups based on the following adverse clinicopathologic features: extracapsular extension (ECE)/neck soft tissue extension (STE), oral cavity primary, microsopically positive margins, nerve invasion, >1 neck nodes, >1 positive nodal groups, node size >3cm, and >6 week interval between surgery and radiation. Patients with none of these factors were defined as low risk and received no further treatment after surgery (n=31). Patients with one adverse factor other than ECE/STE were defined as intermediate risk and received lower dose (57.6 Gy) standard fractionation postoperative RT (n=31). Patients with two or more factors or ECE/STE were defined as high risk and were randomized to higher dose (63 Gy) standard fractionation versus higher dose (63 Gy) altered fractionation with a concomitant boost technique. This shortened the RT treatment time from 7 weeks to 5 weeks. The median followup for the entire group was 59 months.

Results:

Local-regional control at 4 years was better for the low risk (90%) and intermediate risk (94%) patients than the high risk patients (68%).

Overall survival at 4 years was better for the low and intermediate risk groups (83% and 66%) than for the high risk group (43%).

For the high risk patients, interval from surgery to postoperative RT was a significant predictor of local-regional control and overal survival for the 7 week arm, but not for the 5 week arm.

Overall treatment time (surgery plus postoperative radiation therapy) had a significant impact on local-regional control and overall survival, favoring the shorter treatment times. - Acute side effrects were significantly more common in the 5 week arm than the 7 week arm (62% versus 36%). There was no difference in late toxicity between the two arms.

Clinical/Scientific Implications:

This study validated the use of risk clusters to help guide recommendations regarding postoperative radiation therapy.

Overall treatment time appears to be an important factor in treating high risk, postoperative head and neck cancer patients.

Shorter treatment times using a concomitant boost technique can be achieved without dramatically increasing late toxicity. Future directions for improving the outcomes of high risk, postoperative patients may include the addition of chemotherapy or shortening the interval from surgery to postoperative radiation therapy.